Triazolo [4,3-c]pyrimidines substituted by nitrogen-containing heterocyclic rings

Abstract

1,2,4-Triazolo[4,3-c]pyrimidines substituted at the 5 or 7 position through a nitrogen atom which is part of a heterocyclic ring have been found to have potent bronchodilator activity and to be useful synthetic intermediates in the preparation of 1,2,4-triazolo[1,5-c]-pyrimidines. Methods for inducing bronchodilation, pharmaceutical compositions, and synthetic processes and intermediates are also described.

What is claimed is: 
     
       1. A compound of the formula: ##STR95## wherein R 3  is hydrogen or lower alkyl; one of R 5  and R 7  is the heterocyclic substituent ##STR96## wherein X is oxygen, sulfur, sulfinyl, sulfonyl, methylene, imido or N-lower alkylimido; when R 5  is said heterocyclic substituent, R 7  is hydrogen or lower alkyl; when R 7  is said heterocyclic substituent, R 5  is hydrogen, lower alkylthio, phenyl or lower alkyl; and R 8  is hydrogen, phenyl or lower alkyl; or a pharmaceutically acceptable salt thereof. 
     
     
       2. A compound according to claim 1, wherein X is sulfur or oxygen. 
     
     
       3. A compound according to claim 2 wherein R 8  is hydrogen. 
     
     
       4. A compound according to claim 1, selected from the group consisting of: 3,5-bis(n-propyl)-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c]-pyrimidine,   5-ethyl-3-methyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c]-pyrimidine,   3-methyl-5-methylthio-8-phenyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c]pyrimidine,   5-ethyl-3-isopropyl-7-(4-thiomorpholino)-1,2,4-triazolo-[4,3-c]pyrimidine,   3-ethyl-5-methyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c]-pyrimidine,   3,5-bis(n-propyl)-7-(4-morpholino)-1,2,4-triazolo[4,3-c]-pyrimidine,   3,5-diethyl-7-(1-piperidino)-1,2,4-triazolo[4,3-c]-pyrimidine,   3-isopropyl-7-(4-morpholino)-5-n-propyl-1,2,4-triazolo[4,3-c]pyrimidine,   7-(4-morpholino)-5-methylthio-1,2,4-triazolo[4,3-c]-pyrimidine,   3-ethyl-5-n-propyl-7-(4-thiomorpholino)-1,2,4-triazolo-[4,3-c]pyrimidine,   7-(4-methyl-1-piperazino)-5-(n-propyl)-1,2,4-triazolo[4,3-c]-pyrimidine,   5-n-propyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c]-pyrimidine,   5-ethyl-7-(4-morpholino)-1,2,4-triazolo[4,3-c]pyrimidine,   5-ethyl-2-methyl-7-(4-morpholino)-1,2,4-triazolo[4,3-c]-pyrimidine, and   3,5-diethyl-7-(4-thiomorpholino)-1,2,4-triazolo[4,3-c]-pyrimidine.   
     
     
       5. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 and a pharmaceutically acceptable vehicle. 
     
     
       6. A method for obtaining bronchodilation in a mammal, comprising administering an effective amount of a compound according to claim 1 to said mammal. 
     
     
       7. A method according to claim 6, wherein said compound is administered orally.